PMID- 10901443
OWN - NLM
STAT- MEDLINE
DCOM- 20001025
LR  - 20141120
IS  - 0196-3635 (Print)
IS  - 0196-3635 (Linking)
VI  - 21
IP  - 4
DP  - 2000 Jul-Aug
TI  - Presence of NMDA receptor subunits in the male lower urogenital tract.
PG  - 566-78
AB  - Some sexual responses in the male rat, specifically penile erection, are 
      controlled by neural circuits in the brain and spine that are stimulated by the 
      binding of excitatory amino acids (EAAs) to the postsynaptic N-methyl-D-aspartate 
      receptor (NMDAR). In the hypothalamus, EAA/NMDAR interaction triggers the 
      activation of neuronal nitric oxide synthase (nNOS) to produce nitric oxide (NO). 
      The local synthesis of this neurotransmitter in the penile nerve terminals causes 
      corpora cavernosal relaxation and erection. During sexual activity, NO is assumed 
      to participate in seminal emission and ejaculation in the prostate and to inhibit 
      voiding reflexes in the bladder. This study aimed to determine in vitro whether 
      NMDAR is present in these organs and whether it affects the tone of tissue strips 
      through an NO-dependent mechanism. We obtained penile, urinary bladder, and 
      ventral prostate tissues from adult male rats and homologous surgical tissues 
      from human male patients. We detected the NMDAR protein by Western blot and 
      determined the binding of the NMDA antagonist, 3H-CGP. The NMDAR messenger 
      ribonucleic acid (mRNA) was detected by reverse transcription/polymerase chain 
      reaction and identified by cloning and sequencing. The in vitro response to NMDAR 
      antagonists was measured in tissue strips that were precontracted with 
      bethanechol or electrical field stimulation (in rat and human bladder), 
      phenylephrine (in human corpora cavernosa), or norepinephrine (in human 
      prostate). The NMDAR2B protein; ligand-binding activity; and NMDAR1, 2A, and 2B 
      mRNAs were detected in all tissues studied. We found an NMDAR1 variant in rat 
      prostate and penis and in human prostate that is larger than its cerebellar 
      counterpart, but it encodes a 767-amino acid truncated protein (NMDAR1-T). The in 
      vitro contraction of tissue strips was inhibited by NMDAR antagonists against the 
      following sites: polyamine (with ifenprodil); ion channnel high affinity (with 
      dizocilpine); ion channel low affinity (with memantidine, dextrometorphan, and 
      ketamine); and, in an NO-independent, nonadrenergic-noncholinergic pathway that 
      was only partially affected by EAAs. We conclude that, in vitro, all the 
      essential NMDAR subunits are present in the lower urogenital tract, a novel 
      variant of subunit 1 is expressed, the tissues bind an NMDAR ligand, and the 
      NMDAR antagonists induce relaxation of tissue strips. Further work is necessary 
      to determine whether the NMDAR subunits form a fully active receptor and 
      participate in the control of organ tone that is relevant to male sexual 
      activity.
FAU - Gonzalez-Cadavid, N F
AU  - Gonzalez-Cadavid NF
AD  - Department of Urology, University of California at Los Angeles School of 
      Medicine, Harbor-UCLA Medical Center, Torrance 90509, USA. ncadavid@ucla.edu
FAU - Ryndin, I
AU  - Ryndin I
FAU - Vernet, D
AU  - Vernet D
FAU - Magee, T R
AU  - Magee TR
FAU - Rajfer, J
AU  - Rajfer J
LA  - eng
GR  - R01DK53069/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Androl
JT  - Journal of andrology
JID - 8106453
RN  - 0 (Ligands)
RN  - 0 (Protein Isoforms)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
SB  - IM
MH  - Amino Acid Sequence/genetics
MH  - Animals
MH  - Base Sequence/genetics
MH  - Humans
MH  - In Vitro Techniques
MH  - Ligands
MH  - Male
MH  - Molecular Sequence Data
MH  - Muscle Contraction/drug effects
MH  - Muscle, Smooth/drug effects/physiology
MH  - Penis/*metabolism
MH  - Prostate/*metabolism
MH  - Protein Isoforms/antagonists & inhibitors/genetics/metabolism
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/genetics/*metabolism
MH  - Tissue Distribution
MH  - Urinary Bladder/drug effects/*metabolism/physiology
EDAT- 2000/07/20 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/07/20 11:00
PHST- 2000/07/20 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/07/20 11:00 [entrez]
PST - ppublish
SO  - J Androl. 2000 Jul-Aug;21(4):566-78.